Colorectal cancer is globally the third most common type of cancer and the fourth most common cause of cancer death (Parkin et al, 1999; Pisani et al, 1999). Curative surgery is feasible in three-quarters of the patients, but despite this, about one half of the patients subsequently develop incurable recurrent cancer (Galandiuk et al, 1992). Adjuvant chemotherapy or chemoradiation Enzalutamide MDV3100 reduces recurrences and mortality in colorectal cancer (Van Cutsem et al, 2002). Regimens containing 5-fluorouracil (5-FU) and leucovorin (LV) have been considered as standard adjuvant chemotherapy regimens in colorectal cancer (O’Connell et al, 1998; Wolmark et al, 1999; Kerr, 2001), and addition of oxaliplatin to 5-FU and LV appears to further improve efficacy (Andre et al, 2004).
Diarrhoea is one of the most troublesome adverse effects related to cancer chemotherapy. 5-Fluorouracil-, capecitabine-, and irinotecan-based regimens that are commonly used in the treatment of colorectal cancer are frequently associated with diarrhoea. Excessive bowel motility may be reduced using drugs such as loperamide and somatostatin analogues, but these treatments may also be associated with adverse effects, and simple and safe measures to reduce drug-induced diarrhoea are thus needed. The mode of chemotherapy administration may also influence chemotherapy-related toxicity. Regimens where 5-FU is administered as protracted continuous infusions may result in a more favourable toxicity profile including the frequency and severity of diarrhoea as compared to the Mayo regimen, where 5-FU is given as boluses on 5 consecutive days 4-weekly (de Gramont et al, 1997a).
According to a meta-analysis of controlled trials performed on hospitalised children who have acute diarrhoea, co-administration of some microorganisms (probiotics) such as Lactobacillus rhamnosus GG with standard rehydration therapy reduces the duration of diarrhoea (Huang et al, 2002). Some placebo-controlled studies also suggest that probiotics are of benefit in the treatment of antibiotics-associated diarrhoea and in the prevention of nosocomial diarrhoea in infants (Szajewska et al, 2001; Cremonini et al, 2002). The putative mechanisms of L.
rhamnosus GG action may include stimulation of the cell proliferation rate of bowel epithelial cells, enhanced secretion of protective mucins leading to reduced adherence of enteropathogenic bacteria to the bowel wall, inhibition of bacterial translocation into the tissues, and stimulation of local and systemic immune response to pathogens (Mattar et al, 2001; Banasaz et al, 2002; Khaled et al, 2003; Mack et al, 2003; Vaarala, 2003). Partially hydrolysed guar gum fibre may also reduce duration of diarrhoea (Homann et al, 1994; Alam et al, 2000) and prolong the colonic transit GSK-3 time (Meier et al, 1993).